Edythe London, professor of psychiatry in the University of California’s Semel Institute for Neuroscience and Human Behavior, and colleagues report that leptin reduces activation in regions of the brain linked to hunger while enhancing activation in regions linked to inhibition and satiety.

The researcher’s used functional magnetic resonance imaging (fMRI) to measure brain activity before and after leptin supplementation in three adults from a Turkish family who lacked the leptin (ob) hormone due to a mutation. Such a mutation in the ob gene causes leptin deficiency and morbid obesity.

The reason the study only involved three subjects, said London, is because “having a genetic deficiency in leptin is extremely rare, so we were fortunate in finding them.” Indeed, research published in 2005 by Julio Licinio, then at University of California, Los Angeles, used the same three family members to show that when leptin replacement was provided to them, body weight and eating behaviour was normalized.

In order to determine the neural circuits through which leptin alters human feeding behaviour, the researchers showed images of food to the adults both before and after leptin treatment, while fMRI imaging was taking place. After leptin replacement in these individuals, feelings of hunger induced by the images and activity in certain brain regions associated with hunger the insula, parietal, and temporal cortex were reduced, while brain activity increased in the prefrontal cortex, an area of the brain previously associated with feeling full or satisfied.

Despite the limitations in only having three subjects with the ob mutation, said London, “we think knowing the mechanisms by which leptin alters brain function in congenital leptin deficiency can provide understanding of normal leptin physiology. Ultimately, that may help identify new targets for the treatment of obesity and related metabolic disorders.”